IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy

Millar, N. L. et al. (2016) IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy. Scientific Reports, 6, 27149. (doi:10.1038/srep27149) (PMID:27263531) (PMCID:PMC4893609)

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Abstract

Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Akbar, Mr Moeed and Reilly, Mr James and Millar, Dr Neal and Kerr, Mrs Shauna
Authors: Millar, N. L., Akbar, M., Campbell, A. L., Reilly, J. H., Kerr, S. C., McLean, M., Frleta-Gilchrist, M., Fazzi, U. G., Leach, W. J., Rooney, B. P., Crowe, L. A.N., Murrell, G. A.C., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Scientific Reports 6:27149
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
620681The role of microRNA 29 in tendon diseaseNeal MillarWellcome Trust (WELLCOME)100651/Z/12/ZIII -IMMUNOLOGY